| First Author | Kapur M | Year | 2020 |
| Journal | Neuron | Volume | 108 |
| Issue | 1 | Pages | 193-208.e9 |
| PubMed ID | 32853550 | Mgi Jnum | J:297745 |
| Mgi Id | MGI:6479214 | Doi | 10.1016/j.neuron.2020.07.023 |
| Citation | Kapur M, et al. (2020) Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic Transmission and Seizure Susceptibility. Neuron 108(1):193-208.e9 |
| abstractText | The mammalian genome has hundreds of nuclear-encoded tRNAs, but the contribution of individual tRNA genes to cellular and organismal function remains unknown. Here, we demonstrate that mutations in a neuronally enriched arginine tRNA, n-Tr20, increased seizure threshold and altered synaptic transmission. n-Tr20 expression also modulated seizures caused by an epilepsy-linked mutation in Gabrg2, a gene encoding a GABAA receptor subunit. Loss of n-Tr20 altered translation initiation by activating the integrated stress response and suppressing mTOR signaling, the latter of which may contribute to altered neurotransmission in mutant mice. Deletion of a highly expressed isoleucine tRNA similarly altered these signaling pathways in the brain, suggesting that regulation of translation initiation is a conserved response to tRNA loss. Our data indicate that loss of a single member of a tRNA family results in multiple cellular phenotypes, highlighting the disease-causing potential of tRNA mutations. |
